Field of the Invention
The present invention relates to host cells that may be used to prepare mevalonate kinase, mevalonate-5-phosphate, and isoprenoid compounds.
Discussion of the Background
Natural rubber is a very important raw material in tire and rubber industries. While its demand will be expanded in the future due to motorization mainly in emerging countries, it is laborious to increase the number of agricultural farms dedicated to rubber in view of regulation of deforestation and competition with palm plantations. Thus, the balance of demand and supply is predicted to become tight. Synthesized polyisoprene is available as a substitute for natural rubber. Polyisoprene's raw material monomer (isoprene (2-methyl-1,3-butadiene)) is mainly obtained by extracting from a C5 fraction obtained by cracking of naphtha. However in recent years, with the use of light feed crackers, an amount of produced isoprene tends to decrease and reliable supply is a concern. Also in recent years, since variation in oil prices impacts production greatly, there is a need to establish a system in which isoprene derived from non-oil sources is produced inexpensively to stably ensure the supply of isoprene monomer.
In view of such need, a method in which the isoprene monomer is produced using a transformant obtained by introducing an isoprene synthase gene and a mutant thereof derived from isolated kudzu or poplar into a microorganism for fermental production has been described in JP 2011-505841 and JP 2011-518564. It has been described in Yuliya, A., et al., Appl. Environ. Microbiol., vol. 77 (No. 21), pp. 7772-77-78, 2011, that mevalonate kinase, an enzyme in a mevalonate pathway, is inhibited by DMAPP, a metabolite in the mevalonate pathway.
A method of producing an isoprene monomer using a transformant obtained by introducing a mevalonate kinase derived from isolated Methanosarcina mazei into a microorganism for fermental production has been described in WO 2010/031062. Also, a method of producing an isoprene monomer using a transformant obtained by introducing a mevalonate kinase derived from actinomyces or lactobacillus into a microorganism for fermental production has been described in WO 2010/031077.
Further, as described in Martin, V. J., et al., Nature Biotechnology, vol. 21 (No. 7), pp. 796-802, 2003, isoprene is one of the isoprenoids, and a reaction catalyzed by the mevalonate kinase is a rate-limiting step when isoprenoids are produced by fermentation of microorganisms.
Other relevant description can be found in WO 2010/031062, WO 2010/031077, Kesselmeier, J., et al., Journal of Atmospheric Chemistry, vol. 33, pp. 23-88, 1999, Monson, R. K., et al., Plant Physiol., vol. 98, pp. 1175-1180, 1992, and Kuzma, J., et al., Plant Physiol., vol. 101, pp. 435-440, 1993.